Lombardi Maria Stella, Kavelaars Annemieke, Heijnen Cobi J
Department of Immunology, University Medical Center Utrecht, The Netherlands.
Crit Rev Immunol. 2002;22(2):141-63.
Many extracellular stimuli, such as neurotransmitters, hormones, chemokines, proteinases, inflammatory mediators, odorants, and light, are recognized by the superfamily of G protein-coupled receptors (GPCRs). Immune cells express GPCRs for classical chemoattractants, chemokines, neuropeptides, and neurotransmitters. GPCRs transmit information by interacting with heterotrimeric G proteins, resulting in rapid and transient signaling. The signal given by GPCRs is terminated rapidly by the activity of regulators of G protein signaling (RGS). In addition, GPCR responsiveness diminishes after repeated or prolonged exposure to the agonist. This process of homologous desensitization of GPCRs is dependent on receptor phosphorylation by G protein-coupled receptor kinases (GRKs). In this review, we describe the role of RGS and GRKs in the regulation of GPCR signaling in the immune system, with special emphasis on the role of changes in GRKs and RGS expression during (auto) immune processes. Since altered regulation of GPCR signaling can influence disease states, the molecules involved in this process can also represent attractive therapeutic targets.
许多细胞外刺激，如神经递质、激素、趋化因子、蛋白酶、炎症介质、气味分子和光，都由G蛋白偶联受体（GPCR）超家族识别。免疫细胞表达用于经典趋化剂、趋化因子、神经肽和神经递质的GPCR。GPCR通过与异源三聚体G蛋白相互作用来传递信息，从而产生快速且短暂的信号传导。GPCR发出的信号通过G蛋白信号调节剂（RGS）的活性迅速终止。此外，在反复或长时间暴露于激动剂后，GPCR的反应性会降低。GPCR的这种同源脱敏过程取决于G蛋白偶联受体激酶（GRK）介导的受体磷酸化。在这篇综述中，我们描述了RGS和GRK在免疫系统中GPCR信号传导调节中的作用，特别强调了GRK和RGS表达变化在（自身）免疫过程中的作用。由于GPCR信号传导调节的改变会影响疾病状态，参与这一过程的分子也可能是有吸引力的治疗靶点。
